The primary objective of this study is to assess the safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with other anticancer drug(s), and to determine the optimal dose of E7386 in combination with lenvatinib in endometrial carcinoma (EC) (for EC Dose Optimization Part only).
The Dose Escalation and Dose Expansion parts of the study have completed enrollment. The Dose Optimization part of the study is enrolling participants with endometrial carcinoma (EC) only.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
301
E7386 dosing.
Lenvatinib dosing.
Doxorubicin dosing.
Paclitaxel dosing.
UAMS
Little Rock, Arkansas, United States
RECRUITINGUniversity of California San Diego (UCSD) - Moores Cancer Center(All)
La Jolla, California, United States
RECRUITINGCedars-Sinai Medical Center
Los Angeles, California, United States
COMPLETEDPasadena Liver Center
Pasadena, California, United States
Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs)
DLTs will be defined as any of the events that are considered by the investigator to be at least possibly related to therapy with the study medication. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0).
Time frame: Cycle 0 (Cycle 0 length=6 or 7 days) up to Cycle 1 (Cycle 1 length=28 days)
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 30 days after the last dose of study drug or before initiating post anti-cancer treatment (up to approximately 90 months)
Dose Optimization Part: Objective Response Rate (ORR) per RECIST 1.1 by Investigator Assessment
The ORR is defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR). The ORR will be assessed by investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for dose optimization part.
Time frame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 90 months)
Dose Escalation Part: Cmax: Maximum Observed Plasma Concentration for E7386
Time frame: Day 1 to Day 8
Dose Escalation Part: Cmax: Maximum Observed Plasma Concentration for Lenvatinib
Time frame: Day 8
Dose Escalation Part: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7386
Time frame: Day 1 to Day 8
Dose Escalation Part: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Lenvatinib
Time frame: Day 8
Dose Escalation Part: AUC: Area Under the Plasma Concentration Versus Time Curve for E7386
Time frame: Day 1 to Day 8
Dose Escalation Part: AUC: Area Under the Plasma Concentration Versus Time Curve for Lenvatinib
Time frame: Day 8
Dose Escalation Part: CL/F: Apparent Total Body Clearance for E7386
Time frame: Day 1 to Day 8
Dose Escalation Part: CL/F: Apparent Total Body Clearance for Lenvatinib
Time frame: Day 8
Dose Escalation Part: Vz/F: Apparent Volume of Distribution for E7386
Time frame: Day 1 to Day 8
Dose Escalation Part: Vz/F: Apparent Volume of Distribution for Lenvatinib
Time frame: Day 8
Percentage of Participants with Best Overall Response (BOR)
BOR is defined as confirmed CR, confirmed PR, stable disease (SD), PD, and not evaluable (NE). The BOR will be assessed by investigator based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC subparts in dose escalation part and based on RECIST version 1.1 for ST subparts in dose escalation part, and for HCC subpart, CRC subpart, EC subpart in dose expansion part and in dose optimization part.
Time frame: From first dose of study drug until progression of disease (PD), development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 90 months)
Objective Response Rate (ORR)
The ORR is defined as the percentage of participants with a BOR of CR or PR. The ORR will be assessed by investigator based on mRECIST for HCC subparts in dose escalation part and based on RECIST version 1.1 for ST-subparts in dose escalation part, and for HCC subpart, CRC subpart, EC subpart in dose expansion part.
Time frame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 90 months)
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a BOR of CR, PR, or SD. The DCR will be assessed by investigator based on mRECIST for HCC subparts in dose escalation part and based on RECIST version 1.1 for ST-subparts in dose escalation part, and for HCC subpart, CRC subpart, EC subpart in dose expansion part and in dose optimization part.
Time frame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 90 months)
Clinical Benefit Rate (CBR)
The CBR is defined as the percentage of participants with a BOR of CR, PR, or durable SD. The CBR will be assessed by investigator based on mRECIST for HCC subparts in dose escalation part and based on RECIST version 1.1 for ST-subparts in dose escalation part, and for HCC subpart, CRC subpart, EC subpart in dose expansion part and in dose optimization part.
Time frame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 90 months)
Progression-free Survival (PFS)
PFS is defined as the time from the date of the first dose to the date of the first documentation of confirmed PD or death, whichever occurs first. The PFS will be assessed by investigator based on mRECIST for HCC subparts in dose escalation part and based on RECIST version 1.1 for ST-subparts in dose escalation part, and for HCC subpart, CRC subpart, EC subpart in dose expansion part and in dose optimization part.
Time frame: From first dose of study drug until PD, or death from any cause, whichever occurs first (up to approximately 90 months)
Overall Survival (OS)
OS is defined as the time from the first dose of study drug to death due to any cause. OS will be calculated for all subparts in dose expansion part, dose optimization part, and HCC subparts in dose escalation part only.
Time frame: From first dose of study drug until death from any cause (up to approximately 90 months)
Duration of Response (DOR)
DOR is defined as the time from the first documentation of PR or CR to the first documentation of disease progression or death due to any cause (whichever occurs first). DOR will be calculated for all subparts in dose expansion part, dose optimization part, and HCC subparts in dose escalation part only.
Time frame: From first dose of study drug until PD, or death from any cause, whichever occurs first (up to approximately 90 months)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
California Pacific Medical Center
San Francisco, California, United States
RECRUITINGUCLA University of California - Los Angeles
Santa Monica, California, United States
ACTIVE_NOT_RECRUITINGJohn Muir Clinical Research
Walnut Creek, California, United States
RECRUITINGUniversity of Colorado Cancer Center - Anschutz Medical Campus
Aurora, Colorado, United States
RECRUITINGUni. Of Miami- Sylvester Cancer Centre
Miami, Florida, United States
RECRUITINGFlorida Cancer Specialists - South
Sarasota, Florida, United States
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